A case report of drug interaction between co-packaged nirmatrelvir-ritonavir and tacrolimus causing hyponatremia in a lung transplant recipient.

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection in lung transplant recipients can be lethal owing to the use of immunosuppressants. Antiviral agents may be administered to these patients. Co-packaged nirmatrelvir-ritonavir is a new agent currently being used in combination. CASE PRESENTATION: In this report, we present a case of a 64-year-old woman, a lung transplant recipient, who experienced hyponatremia and showed a high serum tacrolimus concentration following the administration of the co-packaged nirmatrelvir-ritonavir combination. CONCLUSION: Although the nirmatrelvir-ritonavir and tacrolimus combination is not contraindicated, other treatment strategies should be considered first, if available, and the dose of tacrolimus should be reduced when using the nirmatrelvir-ritonavir combination. In cases where combination therapy is necessary, serum tacrolimus levels should be closely monitored in lung transplant recipients. Documentation of more such reports is important to identify drug interactions between nirmatrelvir-ritonavir and other agents, with the aim of preventing severe adverse effects.

Severe hyponatremia and diabetes insipidus caused by low-dose cyclophosphamide in breast cancer patients: A case report and literature review.

RATIONALE: Cyclophosphamide (CTX) is widely used in the treatment of malignancies and autoimmune diseases. Although severe hyponatremia caused by low-dose CTX chemotherapy is uncommon, it can lead to serious complications and even death. PATIENT CONCERNS: A 44-year-old woman with left-sided breast cancer suddenly experienced headaches, disorientation and weakness after receiving low-dose neoadjuvant chemotherapy combined with CTX and doxorubicin. DIAGNOSES: The patient pathology showed invasive breast carcinoma. She developed severe hyponatremia and a generalized seizure after completing the first cycle of neoadjuvant chemotherapy with CTX and doxorubicin. Laboratory tests showed a serum sodium of 118 mmol/L (normal range 135-145 mmol/L) and potassium sodium 3.16 mmol/L (normal range 3.5-5.5 mmol/L). Subsequently, the patient developed secondary diabetes insipidus 4 hours after sodium supplementation, her 24-hour urine volume was 4730 mL (normal range 1000-2000 mL/24 hours), and the urine specific gravity decreased to 1.005. INTERVENTIONS: The patient was given intravenous sodium chloride (500 mL of 3%NaCl, 100 mL/hour) and potassium chloride (500 mL of 0.3%KCl, 250 mL/hour). Meanwhile, she was advised to reduce her water intake, and pituitrin was administered to prevent dehydration caused by diabetes insipidus. OUTCOMES: The patient completely recovered after correcting of the serum sodium concentration (137 mmol/L) without any neurological deficits. After discontinuing pituitrin, her 24-hour urine volume was 2060 mL and the urine specific gravity was 1.015. LESSONS: This is a typical case of severe hyponatremia induced by low-dose CTX. Clinicians and healthcare providers should be aware of this potential toxicity, and appropriate monitoring should be implemented.

The risk of antidepressant-induced hyponatremia: A meta-analysis of antidepressant classes and compounds.

BACKGROUND: Hyponatremia (hypoNa) is a potentially serious adverse event of antidepressant treatment. Previous research suggests the risk of drug-induced hyponatremia differs between antidepressants. This meta-analysis sought to determine the risk of antidepressant-induced hypoNa, stratified by different compounds and classes. METHODS: A PRISMA-compliant systematic search of Web of Science and PubMed databases was performed from inception until Jan 5, 2023, for original studies reporting incidences or risks of hypoNa in adults using antidepressants. We modelled random-effects meta-analyses to compute overall event rates and odds ratios of any and clinically relevant hypoNa for each compound and class, and ran head-to-head comparisons based on hypoNa event rates. We conducted subgroup analyses for geriatric populations and sodium cut-off value. The study is registered with PROSPERO, CRD42021269801. RESULTS: We included 39 studies (n = 8,175,111). Exposure to antidepressants was associated with significantly increased odds of hypoNa (k = 7 studies, OR = 3.160 (95%CI 1.911-5.225)). The highest event rates were found for SNRIs (7.44%), SSRIs (5.59%), and TCAs (2.66%); the lowest for mirtazapine (1.02%) and trazodone (0.89%). Compared to SSRIs, SNRIs were significantly more likely (k = 10, OR = 1.292 (1.120 - 1.491), p < 0.001) and mirtazapine significantly less likely (k = 9, OR = 0.607 (0.385 - 0.957), p = 0.032) to be associated with hypoNa. CONCLUSION: Our meta-analysis demonstrated that, while no antidepressant can be considered completely risk-free, for hypoNa-prone patients mirtazapine should be considered the treatment of choice and SNRIs should be prescribed more cautiously than SSRIs and TCAs.

Eslicarbazepine-induced hyponatremia: A retrospective single-center real clinical practice study.

Hyponatremia is a typical side effect of antiseizure drugs from the dibenzazepine family. The study investigated the prevalence of hyponatremia in patients with epilepsy who were treated with eslicarbazepine. We aimed to determine the prevalence of hyponatremia, reveal the factors leading to the discontinuation of treatment, and identify possible risk factors for the development of hyponatremia including the dose dependency. The medical records of 164 patients with epilepsy taking eslicarbazepine in our center were analyzed. The overall prevalence of hyponatremia was 30.5%. The prevalence of mild hyponatremia, seen in 14%-20% of patients, was not dose dependent. The prevalence of moderate and severe hyponatremia was significantly dose dependent. The severity of hyponatremia was significantly dose dependent. Severe hyponatremia was found in 6.1% of patients. Hyponatremia was asymptomatic in the majority of cases, and in 48% did not require any management. Hyponatremia was the reason for discontinuation in 6.2% of patients. The major risk factor for developing hyponatremia was older age. The study shows that eslicarbazepine-induced hyponatremia is usually mild and asymptomatic. It usually does not require any management and seldom leads to treatment discontinuation. Hyponatremia is dose dependent. Another major risk for developing hyponatremia (besides dose) is older age.

Desmopressin to prevent and treat bleeding in pregnant women with an inherited bleeding disorder: a systematic literature review.

BACKGROUND: Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties. OBJECTIVES: We aimed to review the safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery. METHODS: Databases were searched for articles up to July 25, 2022, reporting maternal and/or neonatal outcomes. PRISMA methodology for systematic reviews and meta-analyses was followed (PROSPERO CRD42022316490). RESULTS: Fifty-three studies were included, comprising 273 pregnancies. Regarding maternal outcomes, DDAVP was administered in 73 women during pregnancy and in 232 during delivery. Safety outcome was reported in 245 pregnancies, with severe adverse events reported in 2 (1%, hyponatremia with neurologic symptoms). Overall, DDAVP was used as monotherapy in 234 pregnancies, with effectiveness reported in 153 pregnancies (82% effective; 18% ineffective). Regarding neonatal outcomes, out of 60 pregnancies with reported neonatal outcomes after DDAVP use during pregnancy, 2 children (3%) had a severe adverse event (preterm delivery n = 1; fetal growth restriction n = 1). Of the 232 deliveries, 169 neonates were exposed to DDAVP during delivery, and in 114 neonates, safety outcome was reported. Two children (2%) experienced a moderate adverse event (low Apgar score n = 1; transient hyperbilirubinemia not associated with DDAVP n = 1). CONCLUSION: DDAVP use during pregnancy and delivery seems safe for the mother, with special attention to the occurrence of hyponatremia and for the child, especially during delivery. However, due to poor study designs and limited documentation of outcomes, a well-designed prospective study is warranted.

Precipitation of hyponatremia and seizures by esmolol in sterile water formulation.

PURPOSE: Acute hyponatremia can lead to severe neurological symptoms such as confusion, obtundation, seizures, coma, and respiratory depression, contributing to increased morbidity and mortality. Patients with acute hyponatremia should be evaluated based on volume status and serum osmolality to determine potential causes and appropriate treatment. The aim of this case report is to illustrate the importance of using a multidisciplinary approach to evaluate medication formulation and the potential impact on a patient's clinical course. SUMMARY: A 34-year-old male was admitted for type A aortic dissection and was treated with an esmolol infusion and underwent operative repair. Two days after initiation of esmolol, the patient developed seizures and antiepileptics were initiated. The patient's serum sodium concentration was found to have decreased by a total of 14 mEq/L since admission. The patient had received more than 6 L of esmolol formulated in sterile water over the course of 2 days. The esmolol infusion was converted to another antihypertensive agent, and 0.9% sodium chloride injection was initiated, after which the serum sodium concentration began to recover. No further seizures were observed on continuous electroencephalography, and all antiepileptic drugs were discontinued with no seizure activity. CONCLUSION: The esmolol product utilized in this case was formulated in 250 mL of sterile water, which is suspected to have contributed to the patient's hyponatremia. It is important to be aware of the formulation and excipients of medications and their potential for adverse effects.

High Osmol Gap Hyponatremia Caused by Icodextrin: A Case Series Report.

Recently, hyperosmolar hyponatremia following excessive off-label use of two exchanges of 2 L icodextrin daily during peritoneal dialysis (PD) was reported. We encountered a cluster of 3 cases of PD patients who developed hyperosmolar hyponatremia during on-label use of icodextrin. This appeared to be due to absorption of icodextrin since after stopping icodextrin, the serum sodium level and osmol gap returned to normal, while a rechallenge again resulted in hyperosmolar hyponatremia. We excluded higher than usual concentrations of specific fractions of dextrins in fresh icodextrin dialysis fluid (lot numbers of used batches were checked by manufacturer). We speculate that in our patients, either an exaggerated degradation of polysaccharide chains by α-amylase activity in dialysate, lymph, and interstitium and/or rapid hydrolysis of the absorbed larger degradation products in the circulation may have contributed to the hyperosmolality observed, with the concentration of oligosaccharides exceeding the capacity of intracellular enzymes (in particular maltase) to metabolize these products to glucose. Both hyponatremia and hyperosmolality are risk factors for poor outcomes in PD patients. Less conventional PD prescriptions such as off-label use of two exchanges of 2 L icodextrin might raise the risk of this threatening side effect. This brief report is intended to create awareness of a rare complication of on-label icodextrin use in a subset of PD patients and/or PD prescriptions.

Desmopressin Dose Requirements in Adults with Congenital and Acquired Central Diabetes Insipidus.

Central diabetes insipidus is a rare disorder characterized by a deficiency of vasopressin. The first line drug to treat this disorder is a synthetic analogue of vasopressin, desmopressin.The primary aim of this retrospective register study was to compare desmopressin dose requirements in patients with acquired and congenital DI, and secondly to assess the influence of BMI on dose requirement and risk of hyponatremia with different drug administrations. We included all patients with suspected DI attending the endocrine department at Rigshospitalet, Copenhagen, Denmark in 2022. We identified 222 patients who were included whereof 130/222 (58.6%) were females and median age was 53 years (IQR 35 to 63). The etiology included 7/222 (3.2%) congenital and 215/222 (96.8%) acquired. After converting nasal and sublingual doses to equivalent oral doses, the median daily dose requirement was 600 µg in patients with congenital etiology compared to 200 µg in patients with acquired etiology (p=0.005). We found no association between BMI and desmopressin dose requirements (p=0.6). During the past 12 months, 66/215 (30.7%) had sodium levels<136 mmol/l including 20/215 (9.3%) with sodium levels<131 mmol/l. No increased risk of hyponatremia was found, when nasal and oral were compared (p=0.9). Daily desmopressin dose requirements were higher in patients with congenital DI compared to patients with acquired DI. However, this result was associated with uncertainty due to the small congenital group. BMI did not influence daily dose requirements and nor did type of administration influence the risk of hyponatremia.

Genetic polymorphisms as predictive biomarkers of adverse events during preoperative chemotherapy in esophageal cancer.

PURPOSE: This study aimed to explore associations between genetic polymorphisms and adverse effects due to preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer. METHODS: Preoperative DCF (docetaxel, 70 mg/m2/day, day 1; cisplatin, 70 mg/m2/day, day 1; fluorouracil, 750 mg/m2/day, days 1-5) was repeated every 3 weeks for up to three cycles. Genotyping of nine candidate genetic polymorphisms was conducted using blood samples from the enrolled patients. RESULTS: According to a multivariable analysis evaluating 50 patients, grade 3 or worse neutropenia was more likely to occur in those with the ABCC2-24C/T or T/T genotype (rs717620) (OR, 5.30, P = 0.013). Additionally, patients with the TYMS 3'-UTR 0 bp/0 bp genotype (rs151264360) showed a trend toward grade 3 or worse hyponatremia (OR, 0.16, P = 0.005). Grade 2 or worse thrombocytopenia was more likely to occur in patients with the TNF-α-1031C/T or T/T genotype (rs1799964) (OR, 6.30, P = 0.016) and IL-6-634C/C genotype (rs1800796) (OR, 0.18, P = 0.034), and grade 2 or worse anemia was more likely to occur in patients with the MCP-1-2518G/G genotype (rs1024611) (OR, 0.19, P = 0.027). CONCLUSIONS: ABCC2-24C > T (rs717620), TYMS 3'-UTR 6-bp indel (rs151264360), TNF-α-1031T > C (rs1799964) as well as IL-6-634G > C (rs1800796), and MCP-1-2518A > G (rs1024611) polymorphisms might serve as independent and predictive biomarkers for neutropenia, hyponatremia, thrombocytopenia, and anemia, respectively, during preoperative chemotherapy with docetaxel, cisplatin, and fluorouracil for patients with esophageal cancer.

Cumulative Incidence of Thiazide-Induced Hyponatremia : A Population-Based Cohort Study.

BACKGROUND: According to drug labels, the frequency of thiazide-induced hyponatremia is unknown or uncommon to very rare (that is, <1 in 10 000 to <1 in 100), but the exact burden remains unclear. OBJECTIVE: To estimate the increase in the cumulative incidence of hyponatremia using thiazide diuretics compared with nonthiazide antihypertensive drugs in routine clinical practice. DESIGN: Population and register-based cohort study using target trial emulation. SETTING: Denmark, 1 January 2014 to 31 October 2018. PARTICIPANTS: Two target trials were emulated among persons aged 40 years or older who had no recent prescription for any antihypertensive drug, had no previous hyponatremia, and were eligible for the studied antihypertensive treatments. The first target trial emulation compared new use of bendroflumethiazide (BFZ) versus a calcium-channel blocker (CCB). The second target trial emulation compared new use of hydrochlorothiazide plus a renin-angiotensin system inhibitor (HCTZ-RASi; that is, combination pill) versus a RASi alone. MEASUREMENTS: Two-year cumulative incidences of sodium levels less than 130 mmol/L using stabilized inverse probability of treatment-weighted survival curves. RESULTS: The study compared 37 786 new users of BFZ with 44 963 of a CCB and 11 943 new users of HCTZ-RASi with 85 784 of a RASi. The 2-year cumulative incidences of hyponatremia were 3.83% for BFZ and 3.51% for HCTZ-RASi. The risk differences were 1.35% (95% CI, 1.04% to 1.66%) between BFZ and CCB and 1.38% (CI, 1.01% to 1.75%) between HCTZ-RASi and RASi; risk differences were higher with older age and higher comorbidity burden. The respective hazard ratios were 3.56 (CI, 2.76 to 4.60) and 4.25 (CI, 3.23 to 5.59) during the first 30 days since treatment initiation and 1.26 (CI, 1.09 to 1.46) and 1.29 (CI, 1.05 to 1.58) after 1 year. LIMITATION: The study assumed that filled prescriptions equaled drug use, and residual confounding is likely. CONCLUSION: Treatment initiation with thiazide diuretics suggests a more substantial excess risk for hyponatremia, particularly during the first months of treatment, than indicated by drug labeling. PRIMARY FUNDING SOURCE: Independent Research Fund Denmark.

Syndrome of inappropriate antidiuretic hormone secretion as an adverse reaction of ciprofloxacin: a case report and literature review.

Antidiuretic hormone (ADH) is secreted by the posterior pituitary gland. Unsuppressed release of ADH leads to hyponatremia. This condition is referred to as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Hereby, a case report is presented on ciprofloxacin-induced SIADH. A 67-year-old male patient was examined in the emergency room with symptoms of lethargy, headache, lack of attention, and a generally depressed mood lasting for three days. One week prior, empirical antimicrobial therapy involving ciprofloxacin for prostatitis was initiated. Laboratory analysis showed no relevant abnormalities except for hyponatremia (Na = 129 mmol/L). Chronic hyponatremia, thyroid dysfunction, and adrenal dysfunction were ruled out. Serum osmolality was 263 mOsmol/kg, urine osmolality was 206 mOsmol/kg, and urine sodium was 39 mmol/L. Given that all criteria for SIADH were met, ciprofloxacin was discontinued, and fluid restriction was advised. Four days later, the patient's serum sodium concentrations nearly normalized (Na = 135 mmol/L), and all symptoms resolved. The Naranjo Scale yielded a score of 8, supporting the likelihood of a probable adverse reaction to ciprofloxacin. This case is presented to raise awareness among clinicians about the potential of ciprofloxacin to cause even mild hyponatremia.

Thiazide-associated hyponatremia increases the risk of major adverse cardiovascular events among elderly Taiwanese patients.

BACKGROUND: Thiazide-associated hyponatremia (TAH) has been supposed to increase the risk of major adverse cardiovascular events (MACE) in the elderly. Therefore, this study aimed to evaluate the association of TAH with the risk of MACE in elderly Taiwanese patients. METHODS: Data from the longitudinal generation tracking database (LGTD 2010) of the Health and Welfare Data Science Center (HWDC) were retrospectively assessed. The TAH study group was defined as using > 30 cumulative daily defined doses (CDDDs) thiazide diuretics within one year before diagnosis of hyponatremia. The control group (1:3 propensity score matching) had no diagnosis of hyponatremia but had used > 30 CDDDs thiazide diuretics within one year. Data on MACE were extracted using International Classification of Diseases codes. Outcomes were assessed using a multivariable Cox proportional hazard model and Kaplan-Meier analysis. RESULTS: A total of 1155 and 3465 individuals were enrolled in the TAH and the control groups, respectively. The rates of MACE (11.1% vs. 7.3%) and death (22.8% vs.12.2%) were significantly higher in the TAH group than the control group. In the TAH group, the adjusted HRs were 1.29 (CI 1.01 ‒ 1.65) for MACE, 1.39 (CI 1.19 ‒ 1.63) for all-cause death, and 1.61 (CI 0.90 ‒ 2.92) for stroke. CONCLUSION: TAH in patients above 65-years-old is associated with a 29% higher risk of MACE, 39% higher risk of all-cause death, and 61% higher risk of stroke. This work suggests that thiazides prescription in elderly patients should be more careful. However, further research is required to confirm our findings.

A prospective phase II randomized study of docetaxel combined with lobaplatin versus TPF regimen induction chemotherapy followed by concurrent chemoradiotherapy for locally advanced head and neck squamous cell carcinoma.

PURPOSE: To compare the toxicity and clinical efficacy of TL (docetaxel + lobaplatin) induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy and TPF (docetaxel + cisplatin + 5-fluorouracil) induction chemotherapy combined with cisplatin concurrent chemoradiotherapy in the treatment of locally advanced head and neck squamous cell carcinoma. METHODS AND PATIENTS: In total, 128 patients with locally advanced head and neck cancer were prospectively enrolled between August 2016 and April 2021. They were randomly divided into trial group and control group, all using chronological dosage mode. The trial group used TL regimen induction chemotherapy combined with lobaplatin concurrent chemoradiotherapy; the control group used TPF regimen induction chemotherapy and cisplatin concurrent chemotherapy. The endpoints were adverse events and survival rates at 1, 3 and 5 years. RESULTS: Median follow-up was 42 months (20-71 months). (1) Adverse events: During induction chemotherapy, compared with TPF group, grade 3-4 leukocytes and neutrophils, diarrhea, 1-2 hyperbilirubinemia, nausea / vomiting, oral mucositis, fatigue, anorexia, hyponatremia were significantly lower in TL group (p<0. 05): 6% vs. 35%, 14% vs. 53%, 0% vs. 6%, 15% vs. 40%, 9% vs. 56%, 0% vs. 10%, 3% vs. 13%, 2% vs. 23%, 15% vs. 74%. During chemoradiotherapy, the incidence of hyponatremia, hypokalaemia and grade 1-2 nausea was significantly lower in the TL group (p<0. 05), with 24% vs. 69%, 20% vs. 65% and 24% vs. 44%, respectively. However, more grade 3-4 thrombocytopenia were observed in the TL group (15% vs. 3%, p<0. 05). (2) There was no significant difference in the recent objective response rate (ORR) between patients with TL group and TPF group (p=0.961). (3) There was no statistical difference in 1, 3 and 5 years OS between TL group and TPF group, respectively, (71.0% vs. 67.5%, p=0.573), (56.6% vs. 56.9%, p=0.814), (52.5% vs. 52.9%, p=0.841); 1, 3 and 5 years PFS are: (63.4% vs. 64.0%, p=0.883), (51.1% vs. 54.0%, p=0.705) and (47.3% vs. 45.9%, p=0.887), None of them were significantly different. Multivariate analysis of COX regression showed that T stage (p=0.01) and surgery (p=0.046) were independent factors affecting PFS and OS, respectively. OS subgroup analysis shows that people receiving the TL regimen in postoperative and nodal stage N1 and N2 patients tended to survive longer than those receiving the TPF regimen. CONCLUSION: Patients with postoperative, N1 or N2 stage locally advanced head and neck squamous cell carcinoma (HNSCC) may have more significant clinical benefits when treated with TL regimen. TL regimen has advantages in reducing toxic side effects and can be used as one of the first-line treatment options. TRIAL REGISTRATION: ClinicalTrials.gov (No. NCT03117257).

Comparison of Incidence of Hyponatremia between Linezolid and Vancomycin by Propensity Score Matching Analysis.

Several cases of severe hyponatremia induced by linezolid (LZD) were reported. However, severe infections could also cause hyponatremia by increasing vasopressin secretion. To prove that hyponatremia is associated with LZD rather than infection, we compared the incidence and risk of developing hyponatremia between patients receiving LZD and those receiving vancomycin (VCM). A retrospective, single-center, observational cohort study was conducted in patients aged 18 years or older who received intravenous LZD or VCM for 7 d or longer. Hyponatremia was defined as serum sodium level lower than 134 mEq/L and more than 5% decrease from baseline after treatment initiation. The incidence and risk of developing hyponatremia were analyzed between LZD and VCM groups using chi-square test. Four hundred and fifty patients who satisfied the selection criteria were divided into LZD (n = 97) and VCM groups (n = 353). Significant differences in patient characteristics between LZD and VCM groups were observed before propensity score matching, but no significant differences were found after matching. LZD group showed a significantly higher incidence and risk of developing hyponatremia compared to VCM group both before (LZD: 16.5%, VCM: 5.4%; p < 0.001, odds ratio 3.472 [95% confidence interval (CI) 1.711-7.048]) and after (LZD: 17.8%, VCM: 5.5%; p = 0.020, odds ratio 3.738 [95% CI 1.157-12.076]) propensity score matching. In conclusion, propensity score analyses suggest that the risk of hyponatremia associated with LZD is approximately 3.7-fold higher than that associated with VCM, regardless of patient background.

Phase 1 study of selinexor in combination with salvage chemotherapy in Adults with relapsed or refractory Acute myeloid leukemia.

Selinexor, an oral inhibitor of the nuclear transport protein Exportin-1, shows promising single-agent activity in clinical trials of relapsed/refractory (R/R) acute myeloid leukemia (AML) and preclinical synergy with topoisomerase (topo) IIα inhibitors. We conducted a phase 1, dose-escalation study of selinexor with mitoxantrone, etoposide, and cytarabine (MEC) in 23 patients aged < 60 years with R/R AML. Due to dose-limiting hyponatremia in 2 patients on dose level 2 (selinexor 40 mg/m2), the maximum tolerated dose was 30 mg/m2. The most common grade ≥ 3 treatment-related non-hematologic toxicities were febrile neutropenia, catheter-related infections, diarrhea, hyponatremia, and sepsis. The overall response rate was 43% with 6 patients (26%) achieving complete remission (CR), 2 (9%) with CR with incomplete count recovery, and 2 (9%) with a morphologic leukemia-free state. Seven of 10 responders proceeded to allogeneic stem cell transplantation. The combination of selinexor with MEC is a feasibile treatment option for patients with R/R AML.

Serum Electrolyte and Metabolic Changes During Conditioning of Autologous Hematopoietic Stem Cell Transplantation in Patients with Autoimmune Diseases: A Prospective Study in a Single Institution.

BACKGROUND AND OBJECTIVES: A hematopoietic stem cell transplant (HSCT) includes a conditioning regimen which may cause unwanted metabolic changes. We analyzed the changes in electrolytes, glucose, urea, and glomerular filtration rate in patients with multiple sclerosis (MS) who underwent an autologous HSCT employing the "Mexican method." PATIENTS AND METHODS: Serum and urinary electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were prospectively assessed on days -11, -9, and 0 in a group of 75 patients with MS receiving an autologous HSCT employing the "Mexican method," which includes high doses of both cyclophosphamide (Cy, 200 mg/kg) and rituximab (1000 mg). RESULTS: The median age of the patients was 46 years, with a range of 20-65. Baseline data were defined at day -11 of the HSCT. There were significant changes in serum and urinary electrolytes, which diminished substantially after the delivery of high-dose Cy; 12 patients (16%) developed hyponatremia and 2 had hyponatremia-induced seizures, which resulted in hospital admissions. A comparison of baseline blood metabolites with those obtained after the full Cy dosage (day 0) revealed a significant increase in blood glucose and uric acid levels with an associated decrease in serum calcium, sodium, and potassium levels. The salient findings were drug-induced hyponatremia and hyperglycemia. CONCLUSION: Significant changes in serum electrolytes, blood glucose, creatinine, uric acid, and estimated glomerular filtration rate (eGFR) were observed in patients given autologous HSCT for MS employing high-dose Cy. Some of these changes may have clinical consequences, mainly those derived from iatrogenic hyponatremia. No evidence of damage to renal function was observed at day 0.